Orientador: Guilherme Antonio Moreira de Barros / Resumo: A Síndrome Dolorosa Miofascial (SDM) é considerada um importante problema de saúde pública, podendo, muitas vezes, ser incapacitante e de difícil tratamento. Considerando que, atualmente, o tratamento da SDM é pouco eficaz para o controle da dor, verificamos a necessidade do estudo de novas técnicas e da comparação com as técnicas já existentes. O presente estudo teve como objetivo comparar técnicas de eletroestimulação intramuscular com a técnica de agulhamento seco para o tratamento dessa enfermidade musculoesquelética. Foram estudados 90 pacientes divididos em três grupos. O primeiro grupo foi tratado com agulhamento seco em pontos de gatilhos (PGs), o segundo grupo com eletroestimulação intramuscular de PGs e o terceiro grupo foi tratado com eletroestimulação de pontos motores (PMs) pertencentes ao músculo acometido e/ou o nervo responsável pela inervação desse músculo. O músculo utilizado foi a porção superior do trapézio que é inervado pelo nervo acessório espinal. Foram realizadas sete sessões de tratamento em cada grupo e todos foram avaliados antes e após o término do mesmo. Não houve diferença estatisticamente significativa nos escores de dor da Escala Verbal Numérica (EVN) entre os grupos estudados, apesar de todas as intervenções terem se mostrado eficazes para o tratamento da dor miofascial do músculo trapézio. / Abstract: Myofascial Pain Syndrome (SDM) is considered an important public health problem and can often be disabling and difficult to treat. Considering that, currently, the treatment of SDM is not very effective for pain control, we verified the need to study new techniques and to compare them with existing techniques. The present study aimed to compare intramuscular electrostimulation techniques with the dry needling technique for the treatment of this musculoskeletal disease. Ninety patients were studied, divided into three groups. The first group was treated with dry needles at trigger points (PGs), the second group with intramuscular electrostimulation of PGs and the third group was treated with electrostimulation of motor points (PMs) belonging to the affected muscle and / or the nerve responsible for innervation of that muscle. The muscle used was the upper portion of the trapezius, which is innervated by the spinal accessory nerve. Seven treatment sessions were carried out in each group and all were evaluated before and after the end of the same. There was no statistically significant difference in pain scores on the Numerical Verbal Scale (EVN) between the groups studied, although all interventions have been shown to be effective for the treatment of trapezius muscle myofascial pain. / Doutor

Sepsis is the most common cause of death in the intensive care units worldwide. Despite the undeniable progress in pre- and clinical research, the effective causal therapeutic strategy still does not exist. Given to extremely complex and heterogenic host response to presence of infection, the paradigm "one disease, one drug" is obviously flawed and combination of multiple targets that involves early immunomodulation and cellular protection are needed. Cellular therapy using mesenchymal stem cells represents strategy that brought positive results in experiments with rodent septic models. Part of this thesis is dedicated to evaluation of safety and efficacy of stem cells intravenous administration to well-established large animal model of progressive peritoneal sepsis. Affecting of the neuroinflammatory reflex through the vagus nerve stimulation showed potential to attenuate sepsis in rodents. Rest of the text is dedicated to evaluation of vagus nerve stimulation effectivity in our model. KEYWORDS Sepsis, sepsis-associated acute kidney injury, mesenchymal stem cells, vagus nerve stimulation

The stomach is a digestive organ in the gastrointestinal tract that regulates food intake and paces digestion of nutrients and fluids. The emptying and motility patterns of the stomach are crucial rate-determining processes in maintaining energy homeostasis in the body. Dysregulation of gastric functions often leads to distressing conditions such as gastroesophageal reflux diseases, functional dyspepsia, gastroparesis and obesity. Gastric disorders affect more than 60 million people in the US, producing significant medical and economic burden. These diseases are often chronic and greatly compromise quality of life. As the causes of these diseases remain largely unknown, effects of current pharmacological, dietary, or surgical treatments are often dismal. In this regard, neuromodulation of peripheral nerves emerges as a promising electroceutical therapy for remedying gastric disorders. However, therapeutic effects were shown to be modest, largely due to the inability to validate or calibrate the efficacy and stability of neuromodulation methods with appropriate physiological readouts. To address these problems, here I developed a non-invasive, repeatable online high-resolution magnetic resonance imaging protocol, empowered with advanced image processing algorithms, to track gastric emptying, antral motility, pyloric motility, intestinal filling and absorption in a rat model. The protocol can be used to guide tuning and optimization of stimulation parameters of neuromodulation without perturbing ongoing and spontaneous physiology. The proposed technology and findings are expected to pave the way for the use of gastric MRI to evaluate the efficacy of therapeutics in treating gastric disorders under both preclinical and clinical settings.

Electrical stimulation on nerves is a relatively new area of research and has been proved to speed up recoveryfrom nerve damage. In this work, the efficiency and stability of antennas integrated on printed circuit boards provided by the department of electrical engineering are examined. An automated test bench containing a stepmotor with a slider and an Arduino is created. Different setups were used when measuring on the boards, which resulted in that the largest antenna gave the most stable output despite the distance between transmitterand receiver. The conclusion was that the second best antenna and the smallest one would be suitable as well,and the better choice if it is to be implemented under the skin. A physical setup consisting of LEDs, an Arduino, a computer, and a function generator was created to examinethe voltage control functionality, where colored LEDs were lit depending on the voltage level. The functionality was then implemented in a circuit that in the future shall be integrated on the printed circuit board. To control high voltages a limiter circuit was examined and implemented. The circuit was simulated and tested, with a realization that a feature covering voltage enlargement is needed for the future.

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<p>In this dissertation, we show three approaches towards selective vagus nerve stimulation (VNS). First, we investigated VNS using microelectrode with circle and Vicsek fractal shape. Our rat study shows that fractal microelectrode can activate C-fibers in cervical vagus nerve with higher energy efficiency compared to circle microelectrode. Secondly, we developed stretchable and adhesive cuff device for a compliant neural interface for a long-term stability. We designed Y-shaped kirigami thin-film device for stretchable neural interface and applied a tissue-adhesive hydrogel to enable tough adhesion of the cuff electrode, which can be potentially used to fix the position of microelectrode for a reliable selective stimulation with minimal mechanical mismatch. Lastly, we developed a microchannel electrode array device to potentially measure high-quality of single fiber action potential (SFAP) from the abdominal vagal trunk of rat to explore natural patterns selective organ activities which can be used for a fine-tuned selective VNS. Our results show the potential of measuring C-fiber activities evoked by cervical VNS.</p>

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Vagus nerve stimulation (VNS) treats patients with drug-resistant epilepsy, depression and heart failure, but the mechanisms responsible are uncertain. The mild stimulus intensities used in chronic VNS suggest activation of myelinated primary visceral afferents projecting to the nucleus of the solitary tract (NTS). Here, we monitored the activity of second and higher order NTS neurons in response to peripheral vagal activation using therapeutic VNS criteria. A bipolar stimulating electrode activated the left cervical vagus nerve, and stereotaxically placed single tungsten electrodes recorded unit activity from the left caudomedial NTS of chloralose-anaesthetized rats. High-intensity single electrical stimuli established vagal afferent conduction velocity (myelinated A-type or unmyelinated C-type) as well as synaptic order (second vs. higher order using paired electrical stimuli) for inputs to single NTS neurons. Then, VNS treatment was applied. A mid-collicular knife cut (KC) divided the brainstem from all supramedullary regions to determine their contribution to NTS activity. Our chief findings indicate that the KC reduced basal spontaneous activity of second-order NTS neurons receiving myelinated vagal input by 85%. In these neurons, acute VNS increased activity similarly in Control and KC animals. Interestingly, the KC interrupted VNS activation of higher order NTS neurons and second-order NTS neurons receiving unmyelinated vagal input, indicating that supramedullary descending projections to NTS are needed to amplify the peripheral neuronal signal from VNS. The present study begins to define the pathways activated during VNS and will help to better identify the central nervous system contributions to the therapeutic benefits of VNS therapy. KEY POINTS: Vagus nerve stimulation is routinely used in the clinic to treat epilepsy and depression, despite our uncertainty about how this treatment works. For this study, the connections between the nucleus of the solitary tract (NTS) and the higher brain regions were severed to learn more about their contribution to activity of these neurons during stimulation. Severing these brain connections reduced baseline activity as well as reducing stimulation-induced activation for NTS neurons receiving myelinated vagal input. Higher brain regions play a significant role in maintaining both normal activity in NTS and indirect mechanisms of enhancing NTS neuronal activity during vagus nerve stimulation.

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